| Title: | Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies |
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| Authors: | ID Soler, Miguel, SISSA (Author)
ID De Marco, Ario, UNG (Author)
ID Fortuna, Sara, UNG (Author) |
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| Files: |  Soler_et_al-2016-Scientific_Reports.pdf (1,95 MB)
MD5: 8FFF6923296A39E23851D624572720B9
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| Language: | English |
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| Work type: | Not categorized |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | UNG - University of Nova Gorica
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| Abstract: | Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular
recognition. Their small size represents a precious advantage for rational mutagenesis based on
modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate
mutations by developing a simulation protocol based on all-atom molecular dynamics and wholemolecule
docking. The method was tested on two sets of nanobodies characterized experimentally
for their biophysical features. One set contained point mutations introduced to humanize a wild type
sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae
and human hallmarks. The method resulted in accurate scoring approaches to predict experimental
yields and enabled to identify the structural modifications induced by mutations. This work is a
promising tool for the in silico development of single-domain antibodies and opens the opportunity to
customize single functional domains of larger macromolecules |
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| Keywords: | nanobodies, molecular dynamics, modeling, antibody solubility |
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| Publication version: | Version of Record |
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| Year of publishing: | 2016 |
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| Number of pages: | 11 |
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| Numbering: | 6:34869 | |
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| PID: | 20.500.12556/RUNG-2698  |
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| COBISS.SI-ID: | 4531707 |
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| DOI: | 10.1038/srep34869 |
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| NUK URN: | URN:SI:UNG:REP:LFCPDQKV |
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| Publication date in RUNG: | 11.10.2016 |
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| Views: | 5381 |
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| Downloads: | 249 |
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